The long-range goal of this project is to study the normal early development of glial cell precursors in the telencephalon and the affect on of glial cells by virus, notably the JC virus. Major findings and current studies are: (1) Methods for the study of cellular shape, growth patterns and fine structure during early stages of development were evaluated and modified to meet certain criteria. These methods can be used for electron microscopic, immunocytochemical and in situ hybridization studies of early glial and neuronal development. (2) The neopallial wall and area choroidea in 11-12 day -old fetal rats form a continuous, nonstratified, cohesive monolayer of elongated, radially oriented polarized cells. During the early development of telencephalon, the epithelial character is maintained but modified locally to serve various functions. Of particular interest is that the appearance of cells in area choroidea is similar to that of polarized cells with high metabolic activity elsewhere in the body, e.g., the kidney epithelium. This observation supports a notion that JC virus may enter CNS through the apical surfaces of cells in the choroid area and plexus. 3 The study of two preclinical cases of progressive multifocal leukoencephalopathy (PML) have given new information on the early appearance and progress of PML-lesions in the brain. Cells with capsid-antigen were never seen outside areas of myelin destruction and sections stained for GFAP showed some areas which contained reactive astrocytes but lacked destruction of myelin. The latter finding suggests that reaction of astrocytes as manifestation of disease may exist independently of myelin destruction.